Study Positions SGLT2 Inhibitors as Gout Treatment

A research team at Massachusetts General Hospital has shown that sodium–glucose cotransporter-2 (SGLT2) inhibitors effectively reduce recurrent gout flares in patients with gout and type 2 diabetes and may provide cardiovascular benefits in this patient population.

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"Gout can be acutely painful, and individuals often end up having a lot of flares. Flares can impact quality of life and affect mobility, making it difficult for people to work and even making them bed-bound. In addition, people with gout often have comorbidities such as diabetes, heart disease, metabolic syndrome, and kidney disease, so there is a significant treatment need," says Natalie McCormick, PhD, of the Rheumatology and Allergy Clinical Epidemiology Research Center in the Division of Rheumatology, Allergy and Immunology. "Our study shows that this medication class can prevent recurrent gout flares, including those requiring emergency department visits and hospitalizations."

SGLT2 Inhibitors Reduce Gout Flares

SGLT2 inhibitors are approved for lowering blood sugar in adults with type 2 diabetes. Previous research published in Therapeutic Advances in Chronic Disease has revealed that SGLT2 inhibitors can also lower serum urate levels and provide cardiovascular benefits. The Mass General team decided to compare those specific endpoints between patients taking SGLT2 inhibitors and those taking dipeptidyl peptidase 4 (DPP-4) inhibitors, another second-line glucose-lowering agent.

The team, including Dr. McCormick, Hyon K. Choi, MD, DrPH, director of Clinical Epidemiology and Health Outcomes research in the Division of Rheumatology, Allergy, and Immunology, Chio Yokose, MD, MS, researcher and rheumatologist in the Division, Deborah Wexler, MD, MSc, chief of the Diabetes Unit, and colleagues, examined population data from an administrative database in British Columbia, Canada. The analysis included inpatient and outpatient data on all patients with gout and diabetes who were treated from January 2014 through June 2022. The study, funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, was published in the Annals of Internal Medicine.

"Interestingly, one issue that patients often face when they are first starting urate-lowering therapies is that there can be this paradoxical increase in flares. Our findings did not indicate we had that same issue with individuals starting SGLT2 inhibitors," Dr. McCormick adds.

Initiation of SGLT2 inhibitors was associated with a reduced rate of all types of flares, whether they were identified from inpatient or outpatient data. Among patients taking SGLT2 inhibitors, the flare rate was 52.4 events per 1,000 person-years, compared to 79.7 in patients taking DPP-4 inhibitors. The study also found a reduced risk of myocardial infarction and a tendency toward a reduced risk of stroke.

"We found an even greater reduction in flares that required an emergency department visit or hospitalization," Dr. McCormick says. "And our main findings were consistent with whether or not individuals were taking urate-lowering therapies or whether they were taking diuretic medications at baseline. It was also consistent for different sex and age groups."

The SGLT2 inhibitor group did have an increased risk of genital infections, a known risk with this drug class. The medications can also cause dehydration, Dr. McCormick explains, so patients should be advised and perhaps hold the medication if they have an acute illness or upcoming procedure.

Changing the Paradigm for Gout Treatment

Individuals with gout are often prescribed allopurinol, the most common urate-lowering therapy. But there are adherence challenges with this standard of care. "Although the flares themselves can be quite painful, when people don't have symptoms on a day-to-day basis, they may find it difficult to keep taking the medication long-term," Dr. McCormick posits.

This study doesn't eliminate the need for standard urate-lowering therapies, Dr. McCormick says. However, it positions SGLT2 inhibitors as a strategy to help certain patients as a main treatment or an adjunct therapy. Specifically, she says, in patients with multiple indications, an SGLT2 inhibitor can control diabetes, prevent flares, and reduce the risk of cardiovascular events—all in one medication, which may help improve adherence.

Dr. McCormick and her team hope their findings begin to change the standard of care for patients who have gout combined with other conditions. They are working to spread the word among primary care providers (PCPs) and rheumatologists, who manage the majority of patients with gout.

Expanding SGLT2 Inhibitor Research

The formal indications for SGLT2 inhibitor medications are expanding, and they are now approved for use in some people with heart failure or kidney disease. They are increasingly being used off-label due to their additional benefits.

Dr. McCormick's research group plans to expand their research into the effects of SGLT2 inhibitors in more patient populations, including those without diabetes. This will continue to expand the multidisciplinary nature of their work. In addition to collaborating with PCPs and rheumatologists, they are partnering with endocrinology, cardiology, and nephrology for future projects.

"An interdisciplinary approach was very useful for this research," Dr. McCormick says. "Mass General is an environment where we can reach out and gain expertise from others, which is particularly helpful with these types of patients, who have several comorbidities."

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